The goal of this project is to identify and characterize genes causing birth defects of the limb. Although the etiology of most birth defects remains unknown, a substantial proportion of defects are caused by mutations in genes that are components of developmental programs. Consequently, characterization of the molecular basis of birth defects can reveal the genetic constituents of these developmental programs. To date, we have described the phenotypic spectrum of approximately fifteen different genetic disorders characterized by defects in limb patterning. We have mapped the chromosomal locations of genes causing five of these disorders and identified mutations in genes (TBX3, TBX5, Noggin, and p63) causing 4 of these syndromes.